PROJECT SUMMARY CANDIDATE. Dr. Ruvandhi Nathavitharana, is a physician and Instructor in the Division of Infectious Diseases at Beth Israel Deaconess Medical Center (BIDMC). A 5-year K23 Career Development Award will provide the necessary training and experience needed for her to become an independent investigator in implementation science, with a focus on evaluating and optimizing the impact of tuberculosis (TB) diagnostics. BACKGROUND. TB transmission in health-care facilities in high TB burden countries (HBCs) is a pressing global health problem. A high prevalence of undiagnosed TB has been documented in hospitalized patients in HBCs but TB infection control focuses on patients with known or suspected TB. FAST (Find cases Actively using cough screening and molecular diagnostics, Separate safely and promptly Treat effectively) is an intensified, refocused approach to decrease TB transmission that is being evaluated at Hospital Nacional Hipolito Unanue (HNHU) in Lima, Peru (R01-AI112748, PI: Nardell). FAST improves case detection but is resource intensive due to reliance on a high volume of sputum-based molecular tests. A cost-effective, accurate, non-sputum based triage test is urgently needed to make FAST more feasible in HBCs. RESEARCH. The overall objective for this K23 is to optimize active case finding strategies for TB in health- care facilities in HBCs. The central hypothesis is that a simple, inexpensive, non-sputum based TB triage test with a high sensitivity could have a major clinical impact by improving the performance and sustainability of a transmission reduction strategy like FAST. Using an innovative hybrid study design nested within the parent R01 study, this research will pursue three specific aims: 1) to determine the diagnostic accuracy of three non- sputum based TB triage tests: digital chest x-ray using CAD4TB software (dCXR/CAD4TB), fingerstick C- reactive protein (CRP) and exhaled breath testing (EBT) and determine which patients are missed by cough screening, 2) to evaluate the cost-effectiveness of adding a triage test to FAST and 3) to evaluate the implementation success of these triage tests in the context of FAST at HNHU and consider their potential role in different clinical settings. This research will answer critical questions about the optimization of TB diagnostic testing strategies in healthcare facilities and provide the foundation for an R01 diagnostic intervention trial. MENTORING. Dr. Nathavitharana's primary mentor, Dr. Edward Nardell, is a TB transmission control expert who has an established research partnership in Peru. They have assembled a multi-disciplinary mentoring team across the Harvard network: Dr. Nira Pollock (a physician scientist with diagnostics expertise), Dr. Stephen Resch (a cost-effectiveness expert) and Dr. Lisa Hirschhorn (a physician implementation scientist). TRAINING. The research objectives are supported by a training plan that includes rigorous didactics and coursework on diagnostic evaluation, decision analysis and implementation science, alongside a strong institutional commitment at BIDMC and grant support and development program through Harvard Catalyst.